Traditional disease diagnosis normally begins with a physical examination of the patient's symptoms and a review of the patient's medical and family histories. The diagnosis is usually confirmed as the patient's disease progresses and additional symptoms appear. A proper diagnosis may often times require that laboratory tests be performed in order to provide more detailed information about the patient's condition. In this regard, there are numerous specific tests for different diseases that have been developed and used in modern medicine. Some of the most common tests involve obtaining a blood sample from a patient and examining the sample in the laboratory for both the general and specific diagnostic purposes. Since the circulation of blood is the most significant biochemical transporting and exchanging system in the human body, most illnesses will produce or induce certain changes in the blood's content or its properties. It does not matter whether the human body is exposed to a toxin released from a pathogen or from a pathogen-induced immune response, or whether the body is under the influence of an endocrine system dysfunction or is experiencing nutritional or metabolic problems, all of these abnormal conditions have the potential to induce significant changes in the blood. Therefore, blood samples have become the most commonly collected samples for the laboratory diagnosis and forensic evidence.
Macroscopically, the composition of blood is categorized into two major components: the cellular portion consisting of blood cells, and the fluid portion called plasma. Normally, a blood sample will start to coagulate after being extracted from a blood vessel. The coagulation process involves the aggregation of the blood cells to form a dark solid precipitation. The remaining liquid portion of the blood is called serum. If the blood sample is mixed with an anti-coagulant during or immediately after collection, the blood will not coagulate and will stay in fluid form. If the anti-coagulated blood is centrifuged or kept in a stationary state for a period of time, the blood cells will precipitate. The up-liquid portion of the anti-coagulated blood is the plasma. Depending on the test being conducted, the blood samples are normally collected and used in these three forms: the whole blood, plasma or serum. Most laboratory tests, however, focus on the serum component of coagulated blood.
There are many prior art technologies for detecting changes in blood components and relating the changes as a diagnostic tool to indicate the presence of different diseases. For example, an increase in a patient's white blood cell count generally indicates an inflammation occurring somewhere in the body. A low level hemoglobin number indicates anemia. Without proper medication, diabetes patients will show an abnormal blood glucose level. Therefore, the changes of the blood components are not only resulting from the changes of blood system itself but also can reflect many diseases on other parts of the body. Literally, hundreds of blood components have been identified and used to assist in diagnosing disease. There are still a significant portion of components and functions yet being identified. In this regard, the molecular changes of well-defined markers in the blood are readily detected for many well defined and understood diseases. Most of infectious diseases that induce the immune responses are easily identified by the detection of antibodies in the blood. Unfortunately, for many not well defined physiological illnesses, there are no apparent changes in the body, nor in the blood, until the relatively late stages of the disease. Especially for many kinds of cancer, there is no good marker available.
Genes were originally understood to be the basic molecular unit which controlled inheritance. After the development of the advanced biochemical technology, the chemical structural unit of genes has been revealed to be nucleic acids. Except for a small number of RNA (ribonucleic acid) viruses, genes in all other living organisms are formed from DNA (deoxyribonucleic acid). DNA strands are extremely long and unbranched nucleic acid polymers that contain many different genes in each strand. In living cells, DNA strands fold tightly with certain proteins to form a compact nucleoprotein complex called chromatin. Normally, DNA strands in this form are not active. These sequestered genes can be activated, however, as a result of certain controlled mechanisms that are, in general, not well understood by today's science. Though some studies on the physical structure of the DNA double helix were done in the early stages of DNA analysis by biochemists, biochemistry and molecular biology research done today on the structure and functionality of DNA are mostly confined to an analysis of DNA after it has been almost completely isolated from its nucleoprotein complex.
During the later development stage of molecular biology, the identification of Enhancers, a kind of gene expression regulator, and the discovery of ribozymes have indicated that an analysis of the secondary or tertiary structure of entire nucleic acid complex, beyond just the linear sequence of the nucleic acid units, might have a potentially more important role in the analysis and understanding of gene regulation. The gene rearrangement process in the immune system also has indicated that gene regulation is involved in changes in substantial portions of DNA, instead of just an alteration of a few nucleic acids that only affected a very small portion of entire DNA sequence. Unfortunately, however, due to the extremely long and thin structure of DNA and its dense and compact nucleoprotein complex, it is extremely difficult to isolate the DNA without significantly altering its nucleoprotein complex. Therefore, there is not much known about the structural changes of the nucleoprotein complex. As a result, there is presently no diagnostic tool available which can detect changes in DNA and its associated nucleoprotein complex.
It is well known that white blood cells are responsible for the body's defense system. It is also known that, based upon immunology studies, normal immune response requires about seven (7) days before any specific antibody production clone of a B-lymphocyte can be detected. This fact indicates that the activation of those specific clones of antibody production B-lymphocytes started much earlier, which indicates that the cells responsible for cellular immunity also must have been activated earlier. Unfortunately, these early and delicate changes inside the immunocytes are well below the detectable level of current technology.